Objective:To explore the application value of qualitative characteristics and quantitative parameters of contrast-enhanced ultrasound (CEUS) in the differential diagnosis of pancreatic ductal adenocarcinoma (PDAC) and non-PDAC presenting as pancreatic solid focal lesions.Methods:A retrospective analysis was conducted on 64 cases of PDAC(the PDAC group) and 52 cases of non-PDAC(the non-PDAC group) who underwent CEUS examination at Tianjin Medical University Cancer Institute and Hospital from July 2022 to June 2023. Clinical characteristics, two-dimensional ultrasound features, CEUS qualitative characteristic, and quantitative parameters were compared between the two groups. ROC curves were plotted, and the Delong test was used to evaluate the diagnostic performance of qualitative and quantitative analyses in distinguishing PDAC from non-PDAC. Binary logistic regression analysis was employed to assess the independent predictors of PDAC.Results:①There were significant differences in serum CA19-9, lesion size, boundary, the main pancreatic duct (MPD) diameter, degree of enhancement and enhancement pattern between the PDAC group and the non-PDAC group (all P<0.05). ②The relative peak intensity (rPE), and relative wash-in and wash-out area under the curve (rWiWoAUC) were lower in the PDAC group than the non-PDAC group, with statistically significant differences(all P<0.001). ③The areas under the curve (AUC) for diagnosing PDAC using enhancement pattern, venous phase(VP) enhancement degree, rPE, and rWiWoAUC were 0.698, 0.707, 0.863, and 0.867, respectively. The AUCs of quantitative parameters were superior to those of qualitative characteristics, with statistically significant differences ( P<0.05). Using CEUS mode B, low VP enhancement, rPE<72.44, and rWiWoAUC<86.59 as cut-off values, the accuracies for diagnosing PDAC were 0.698, 0.741, 0.828, and 0.802, respectively. ④Serum CA19-9, lesion size, MPD diameter, rPE, and rWiWoAUC were independent predictors of PDAC (all P<0.05). Conclusions:CEUS qualitative and quantitative analyses are helpful in the differential diagnosis of PDAC and non-PDAC, with rPE and rWiWoAUC being useful indicators for diagnosing PDAC.

Objective:This study aimed to investigate the risk features of postoperative tumor recurrence of medullary thyroid carcinoma.Methods:One hundred and seventy two patients with medullary thyroid carcinoma diagnosed at Tianjin Cancer Hospital between Jan 2010 and Jan 2018 were enrolled in this study. Based on the follow-up results, patients were divided into tumor recurrence and non-tumor recurrence group. US features,clinicopathological characteristics and somatic RET mutations were evaluated between the two groups. The cut-off values of pre-and post-operative serum calcitonin were calculated by ROC curve.Univariate and multivariate analysis were adopted between the two groups to determine independent risk factors for tumor recurrence of MTC.Tumor-free survival was determined by Kaplan-Meier analysis.Results:Univariate analysis showed that preoperative serum calcitonin≥1 367 pg/ml ( χ2=18.909, P=0.000), postoperative serum calcitonin ≥61 pg/ml ( χ2=72.278, P=0.000), mulifocality ( χ2=11.787, P=0.001),lesions in both lobes ( χ2=10.452, P=0.003), extrathyroidal invasion ( χ2=14.511, P=0.000), T3+T4-staging ( χ2=11.920, P=0.001)、TNMⅢ+Ⅳ-staging ( χ2=18.915, P=0.000), ACR TI-RADS 5 ( χ2=7.162, P=0.006) and RET mutation ( χ2=10.937, P=0.001) were significantly related to tumor recurrence of medullary thyroid carcinoma. Multivariate analysis demonstrated that postoperative serum calcitonin≥61 pg/ml ( OR=22.323, 95%CI: 6.370-78.236) and RET mutation ( OR=4.054, 95%CI: 1.354-12.139) were the independent factors related to tumor recurrence of medullary thyroid carcinoma.The survival curves of MTC patients showed a significantly lower percentage of surviving patients in the group with postoperative serum calcitonin ≥61 pg/ml ( P=0.000) or RET mutations ( P=0.001). Conclusions:Postoperative serum calcitonin ≥61 pg/ml and oncogenic RET mutation were the independent risk factors for tumor recurrence of MTC.Patients with postoperative serum calcitonin ≥61 pg/ml or a RET mutation tended to have a shorter tumor-free survival.

Objective:To explore the predictive value of ultrasound-based radiomics for liver metastasis in pancreatic neuroendocrine tumors (pNEN).Methods:A retrospective analysis was conducted on clinical, pathological, and ultrasound data of 269 pNEN patients confirmed by pathology at Tianjin Medical University Cancer Institute and Hospital from January 2012 to June 2022, including 94 patients with liver metastasis and 175 without liver metastasis. The regions of interest (ROI) were delineated on the maximum diameter section of the tumor using ITKSNAP software, and radiomics features were extracted using Pyradiomics. Radiomics features with an intra-group correlation coefficient greater than 0.90 were retained, and the optimal features were selected using the maximum relevance minimum redundancy (MRMR) algorithm. The dataset was randomly divided into a training set and a validation set in a ratio of 7∶3, and the random forest algorithm (Rfs) was used to predict pNEN liver metastasis. Three models were constructed, including the clinical ultrasound model, the radiomics model, and the comprehensive model that combined clinical ultrasound and radiomics features. The predictive performance of different models for pNEN liver metastasis was analyzed using the ROC curve, and the predictive performance of different models was compared using the Delong test.Results:A total of 874 features were extracted from the ROI, and 12 highly robust radiomics features were retained for model construction based on inter- and intra-observer correlation grading and feature selection. The area under curve(AUC), sensitivity, specificity, and accuracy of the radiomics model, the clinical ultrasound model, and the comprehensive model for predicting liver metastasis in pNEN patients were 0.800, 0.574, 0.789, 0.714; 0.780, 0.596, 0.874, 0.777; and 0.890, 0.694, 0.874, 0.810, respectively. The Delong test showed that the comprehensive model had the best predictive performance, with an AUC superior to that of radiomics model ( Z=3.845, P=0.000 12) and clinical ultrasound model ( Z=3.506, P=0.000 45). Conclusions:The radiomics model based on ultrasound has good performance in predicting liver metastasis in pNEN, and the comprehensive model that combines clinical ultrasound and radiomics features can further improve the predictive performance of the model.

Objective:To predict the clinical value of World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading of clear cell renal cell carcinoma (ccRCC) pre-scholarly based on ultrasound imaging group.Methods:Clinical and ultrasound imaging data of patients with surgically pathologically confirmed ccRCC at Tianjin Medical University Cancer Institue and Hospital from January 2021 to October 2022 were retrospectively collected and divided into a low grade group (grade Ⅰ and Ⅱ, 105 cases) and a high grade group (grade Ⅲ and Ⅳ, 70 cases) using WHO/ISUP pathological grading criteria. The clear image of the largest diameter of the tumor was selected and imported into ITK-SNAP software for manual segmentation of the image and extraction of ultrasonographic radiomics features. The patients were randomly divided into a training group and a test group in the ratio of 7∶3, with 122 cases in the training group and 53 cases in the test group. Stable radiomics features were obtained by dimensionality reduction. The support vector machines (SVM) algorithm was applied to predict the pathological grading of ccRCC. Finally, a clinical-ultrasound imaging model, an ultrasonographic radiomics model and a comprehensive model combining the two were constructed. The predictive effects of the three models were analyzed by the area under the ROC curve (AUC). The performance of each model was evaluated by applying the calibration curve. The net benefit of patients was obtained by applying the decision curve.Results:A total of 873 radiomics features were extracted, and 10 features were finally obtained for model construction after dimensionality reduction. Final test results showed that the AUC, sensitivity, specificity and accuracy of the clinical-ultrasound imaging model were 0.68, 0.47, 0.78, 0.66. The AUC, sensitivity, specificity and accuracy of the ultrasonographic radiomics model were 0.74, 0.53, 0.88, 0.74. The AUC, sensitivity, specificity and accuracy of the comprehensive model were 0.84, 0.63, 0.86, 0.77. The AUC of the comprehensive model being larger than that of the clinical-ultrasound imaging model ( Z=-3.224, P=0.001) and ultrasonographic radiomics model ( Z=-2.594, P=0.009). The calibration curves showed that the comprehensive model was more stable than the other two models. The decision curve showed a higher net clinical benefit for the comprehensive model than for the other two models within a threshold of 0.1-1.0. Conclusions:The preoperative prediction of ccRCC pathological grading by the radiomics model based on ultrasound images is effective. The comprehensive model constructed by combining relevant clinical and ultrasound parameters has better performance, which can help predict ccRCC pathological grading preoperatively to a certain extent. It is crucial to help physicians choose the best management plan in the era of personalized medicine.

Objective:To investigate the prediction of National Institute of Healthy (NIH) risk stratification of gastrointestinal stromal tumor(GIST) based on clinical ultrasound model, ultrasonographic radiomics model and combined model by oral contrast enhanced ultrasonography.Methods:The clinical and ultrasound imaging data of 204 gastric GIST patients attending Tianjin Medical University Cancer Institute and Hospital from June 2021 to June 2022 were retrospectively analyzed, among whom a total of 101 patients with high and moderate NIH risk stratification GIST confirmed by postoperative pathology were included in the high risk group, and a total of 103 patients with low and extremely low NIH risk stratification GIST were in the low risk group. The ultrasound images of the largest diameter of the GIST were manually segmented by ITK-SNAP software, and Pyradiomics (v3.0.1) module in Python 3.8.7 was applied to extract ultrasonographic radiomics features from the ROI segmented images. The patients were randomly divided into training and validation sets in the ratio of 7∶3. The XGBoost of Sklearn module was applied to construct the clinical ultrasound imaging model, ultrasonographic radiomics model, and combined model. Then the area under ROC curve (AUC), sensitivity, specificity, and accuracy were evaluated; the predictive ability of the three models was compared by Delong test. Calibration Curve was applied to evaluate the model performance, and the clinical Decision Curve Analysis was applied to determine the net benefit to patients.Results:A total of 578 ultrasonographic radiomics features were extracted from ROI, and 8 ultrasonographic radiomics features were finally retained for modeling after regression and dimensionality reduction. Finally, test results showed that AUC, sensitivity, specificity and accuracy of clinical ultrasound imaging model, ultrasonographic radiomics model and combined model were 0.75, 69.3%, 68.9%, 69.1%; 0.87, 79.2%, 81.6%, 80.4%; 0.91, 80.2%, 83.5%, 81.9%, respectively. Delong test showed that the difference of AUC between ultrasonographic radiomics model and clinical ultrasound imaging model was statistically significant ( Z=2.698, P<0.001), and the combined model was significantly better than clinical ultrasound imaging model ( Z=4.062, P<0.001) and ultrasonographic radiomics model ( Z=2.225, P=0.026). Calibration Curve showed the high performance of combined model, and Decision Curve Analysis showed the superior clinical usefulness of combined model. Conclusions:It is feasible to construct an ultrasonographic radiomics model for GIST NIH risk stratification based on oral contrast enhanced ultrasonography images, and the combined model has more advantageous diagnostic performance, which can identify high risk NIH GIST objectively and stably for clinical purposes.

Objective:To explore the diagnostic value of strain ultrasonic elastography (SUE) supported by Image Pro Plus (IPP) software in distinguishing benign and malignant Breast Imaging Reporting and Data System (BI-RADS) category 4 nodules.Methods:The clinical and ultrasound imaging data of 192 female patients with BI-RADS category 4 nodules diagnosed by breast ultrasound in Tianjin Medical University Cancer Institute and Hospital from January 2020 to January 2021 were retrospectively analyzed. One nodule was selected for each patient, and a total of 192 nodules were analyzed. The ultrasound images and SUE images of each nodule were acquired before surgery, followed by BI-RADS classification scoring and SUE scoring. The IPP software was applied to outline the region of interest of all nodules, and the software automatically counted the SUE area ratio (SUE-IPP-AR) of all nodules. Using pathological diagnosis as the gold standard, SUE-IPP scoring was performed based on the optimal cut-off value of SUE-IPP-AR for distinguishing benign and malignant nodules according to receiver operating characteristic (ROC) curve. The efficacy of BI-RADS classification, SUE score, SUE-IPP score, and SUE-IPP+BI-RADS combined score in the differentiation of benign and malignant breast nodules were analyzed by ROC curve. Kappa coefficient was used to assess inter-observer agreement for SUE and SUE-IPP-AR.Results:Of the 192 nodules, 58 were benign nodules and 134 were malignant nodules diagnosed by pathology. These nodules were classified by BI-RADS, with 46 nodules in BI-RADS category 4A, 57 nodules in BI-RADS category 4B and 89 nodules in BI-RADS category 4C. SUE images 1-6 level were 12, 14, 41, 51, 42, and 32 nodules, respectively. ROC curve analysis showed that the optimal cut-off value of SUE-IPP for determining benign and malignant BI-RADS category 4 breast nodules was 58% [area under the curve (AUC) = 0.729, sensitivity 73%, specificity 69%]. The AUC of SUE-IPP+BI-RADS combined score for determining benign and malignant nodules was the largest (0.871), which was higher than that of BI-RADS score (AUC = 0.829, Z = 2.51, P = 0.012), SUE-IPP score (AUC = 0.729, Z = 3.56, P < 0.001) and SUE score (AUC = 0.695, Z = 4.37, P < 0.001). The sensitivity of SUE-IPP+BI-RADS combined score ≥ 3 points for diagnosing malignant nodules was 86.6%, while the specificity was 82.8%. Therefore, SUE-IPP+ BI-RADS score had the best efficacy for determining benign and malignant nodules. There was good agreement between sonographer with more than 5 years of experience and those with less than 5 years of experience in applying SUE to diagnose breast malignant nodules (Kappa = 0.768, 95% CI 0.711-0.825), and very good diagnostic agreement in applying SUE-IPP (Kappa = 0.946, 95% CI 0.919-0.974). Conclusions:SUE-IPP can improve the diagnostic ability for BI-RADS category 4 breast malignant nodules and can be used as an adjunct to ultrasound diagnosis.

Objective:To evaluate the clinical and ultrasonographic features for early diagnosis and prediction of lateral cervical lymph node metastasis of medullary thyroid microcarcinoma.Methods:From Jan 2010 to Jan 2020 233 patients undergoing primary surgery were categorized as "medullary thyroid microcarcinoma" and "medullary thyroid macrocarcinoma". The preoperative clinical and ultrasonographic characteristics, the diagnostic positive rate of preoperative serum calcitonin and fine needle aspiration (FNA) were investigated between two groups. All patients with medullary thyroid microcarcinoma were divided on the basis of wether there was lateral cervical lymph node metastasis.Results:There were statistically significant differences in initial diagnostic method(χ 2=32.290, P=0.000), TNM staging(χ 2=50.300, P=0.000) between medullary thyroid microcarcinoma and medullary thyroid macrocarcinoma. Medullary thyroid microcarcinoma showed more malignant ultrasonic features. The diagnostic accuracy of preoperative serum calcitonin was higher than FNA for medullary thyroid micro carcinoma(χ 2=47.933, P=0.000). Multivariate regression analysis demonstrated that the abutment/perimeter ≥1/4( OR=25.475, 95%CI: 2.320-279.771), preoperative serum calcitonin >65 ng/L( OR=32.663, 95%CI:2.433-438.409) were the independent factor for lateral cervical lymph node metastases of medullary thyroid microcarcinoma. Conclusions:The combination of ultrasonography and serum calcitonin helps establish early diagnosis of medullary thyroid microcarcinoma. Medullary thyroid microcarcinoma with the abutment/perimeter ≥1/4, serum calcitonin >65 ng/L predicts lateral cervical lymph node metastases.

Objective:To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes.Methods:A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow.Results:In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow ( P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI ( P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference ( P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance ( P=0.858). Conclusions:SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

Objective:To discuss the diagnostic value of superb microvacular imaging (SMI) in renal solid tumors of different sizes.Methods:A total of 142 patients with 146 renal tumors detected by ultrasound in Tianjin Medical University Cancer Institute and Hospital from September 2017 to March 2019 were retrospectively analyzed. The maximum diameter of lesions was 0.8-7.3 cm, and patients were divided into the maximum diameter ≤3.0 cm group (61 patients, 64 lesions) and the maximum diameter >3.0 cm group (61 patients, 82 lesions). All of the tumors were separately evaluated by SMI and color Doppler flow imaging (CDFI) with Adler grade, vascular morphology and peripheral blood flow.Results:In the group with maximum diameter ≤3.0 cm, 50 lesions were malignant and 14 were benign. In the group with maximum diameter >3.0 cm, 62 lesions were malignant and 20 were benign. In the group with maximum diameter ≤3.0 cm, there were no significant differences in location, boundary, echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P>0.05). In the group with maximum diameter >3.0 cm, there were significant differences in echo, homogeneity and small cystic area between malignant tumors and benign tumors ( P<0.05). For all of the benign tumors, there were no significant difference between CDFI and SMI in evaluating Adler grade, vascular morphology and peripheral blood flow ( P>0.05). For malignant tumors with maximum diameter ≤3.0 cm, 43 lesions with Adler grade 2-3 were detected by SMI, which was higher than CDFI (32, P<0.05). There were 38 lesions with dendritic and irregular vascular morphology detected by SMI, which was higher than CDFI (7, P<0.05). The detected rate of peripheral annular or semi-annular blood flow in lesions was 80.0% (40/50), higher than CDFI (18/50, P<0.05). While in malignant tumors with maximum diameter >3 cm, the lesion with peripheral annular or semi-annular blood flow detected by SMI was 38, higher than 22 of CDFI ( P<0.05). The area under the receiver operating characteristic (ROC) curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter ≤3.0 cm was 0.627 (sensitivity: 54.0%, specificity: 71.4%) and 0.791 (sensitivity: 94.0%, specificity: 64.3%), respectively, with statistically significant difference ( P=0.039). The area under the ROC curve for CDFI and SMI diagnosis of renal solid tumors with the maximum diameter>3.0 cm was 0.852 (sensitivity: 85.5%, specificity: 85.0%) and 0.860 (sensitivity: 91.9%, specificity: 80.0%), respectively, without statistically significance ( P=0.858). Conclusions:SMI is superior to CDFI in detecting low-velocity blood flow and microvessels in both malignant and benign renal tumors, and can effectively improve the display rate of peripheral blood flow in malignant tumors. Otherwise, SMI can provide better diagnostic efficiency for renal tumors with the maximum diameter ≤3.0 cm.

Objective:To explore the role of extracellular histones in the pathogenesis of coal worker's pneumoconiosis (CWP) , the relationship of extracellular histones in plasma with pulmonary fibrosis caused by coal mine dust was analyzed, and the stimulating effect of extracellular histones on fibroblast proliferation was studied.Methods:In May 2019, a total of 220 coal mine dust exposure workers (including coal miners and CWP patients) who visited the occupational disease outpatient department of Peking University Third Hospital from 2012 to 2015 were enrolled in the study. According to the classification of small opacity profusion (SOP) in chest radiograph for pneumoconiosis diagnosis (category 0, 1, 2, 3) , 61 coal miners were in category 0 SOP, 65 coal miners were in category 1 SOP, 56 coal miners were in category 2 SOP and 38 coal miners were in category 3 SOP. The plasma levels of extracellular histone H4 and platelet-derived growth factor (PDGF) were measured by enzyme-linked immunosorbent assay (ELISA) kit. The stimulating effects of CWP patients’ plasma and calf thymus histones (CTHs) on fibroblast and the antagonizing effect of anti-H4 antibody were investigated by fibroblast proliferation experiment in vitro.Results:Among the study subjects, there were 195 males (88.6%, 195/220) and 25 females (11.4%, 25/220) , age (55.1±7.2) years, coal mine dust exposure time (16.3±4.4) years. The plasma concentrations of histone H4 in the coal miners with category 0, 1, 2 and 3 SOP were (3.92±1.75) 、(9.84±4.17) 、(14.35±5.52) and (17.83±7.69) μg/ml, respectively. There were significant differences among the four groups ( P<0.01) . The plasma level of histone H4 was positively correlated with the plasma level of PDGF in the coal miners ( r=0.769, P<0.01) . Compared with healthy control plasma group, the cell proliferation percentages of patients' plasma group (272%±87%) and CTH group (283%±84%) were significantly increased ( P<0.05) . Compared with patients' plasma group, the cell proliferation percentage of patients' plasma+anti-H4 antibody group (185%±66%) was significantly decreased ( P<0.05) . Compared with CTH group, the cell proliferation percentage of CTH+anti-H4 antibody group (167%±59%) was significantly decreased ( P<0.05) . Conclusion:Extracellular histones in plasma are associated with pulmonary fibrosis in patients with CWP. Studies in vitro have shown that extracellular histones can promote proliferation of pulmonary fibroblasts. It is suggested that extracellular histones can be important biomarkers for pulmonary fibrosis caused by coal mine dust.